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On Saturday, a San Francisco-based start-up called ZBiotics celebrated the launch of its first product in a fitting way: with a party. The ZBiotics team headed to a Mission District nightclub called Public Works and handed out shot-sized vials of its new probiotic drink. The vials were filled with bacteria that the company had genetically engineered to break down acetaldehyde—a molecule that lingers in the body after alcohol is metabolized.

Biotech’s latest target? The hangover.

ZBiotics began selling the drink online last week. It’s likely the world’s first genetically engineered probiotic, and the start-up isn’t bashful that it’s a genetically-modified organism, or GMO. Remarkably, the company was founded just three years ago and has raised only $3.3 million. The start-up can move fast since its probiotic is considered a food, not a drug, and thus doesn't have to be proven effective in humans.

Numerous other biotech firms have collectively raised hundreds of millions of dollars to engineer or isolate bacteria intended to treat metabolic diseases and cancer. They need that money to conduct clinical trials and ultimately earn approval from the US Food & Drug Administration. ZBiotics is bucking that trend and going straight to consumers.

Zack Abbott, a microbiologist who cofounded the company in 2016, says he had a long list of wild ideas for GMO probiotics, but none of them excited his friends, or investors, as much as a hangover cure. “It really captured people’s imagination, which was exactly what I wanted to do with the technology,” he says.

ZBiotics started with a strain of bacteria, Bacillus subtilis, found in other probiotics and in a traditional Japanese dish of fermented soybeans called nattō. The start-up simply added a gene for acetaldehyde dehydrogenase, the enzyme that breaks down acetaldehyde. Acetaldehyde is linked to the hangover headache, although some studies dispute the connection.

One reason to think that accelerating the breakdown of acetaldehyde would be helpful is what happens when breakdown is blocked. Disulfiram, a drug prescribed to people with alcohol dependence, inhibits acetaldehyde dehydrogenase and causes a person to feel sick after drinking even a small amount of alcohol.

The ZBiotics website jabs at hangover remedies based on plant extracts and nutritional supplements. They are not known to break down acetaldehyde, the firm says, and are unproven in their ability to help with a hangover.

Engineering the bacteria didn’t require the use of CRISPR. Instead, the company relied on an older process called homologous recombination, in which a cell swaps one chunk of DNA out for another. John W. Oliver, the start-up’s head of R&D, calls this “scarless genome editing,” meaning that the final strain is free of any plasmids or antibiotic resistance markers—tools commonly used to create and isolate genetically engineered microbes.

It didn’t take long for ZBiotics to make the designer bug. In fact, the firm has spend most of its existence just testing it. A paper that the firm recently posted on bioRxiv, a site for self-publication of papers that have not yet been peer reviewed, indicates that rats fed the probiotic for 90 days seemed healthy (bioRxiv 2019, DOI: 10.1101/724542). The paper is now undergoing formal peer review at the Journal of Toxicology.

Abbott says the company has been careful to avoid saying its product can prevent, treat, or cure any disease, since that could mean it would have to be regulated as a drug. “There is a reason that we don’t say certain things on the website,” he adds.

According to Abbott, the engineered bacteria readily break down acetaldehyde in test tubes, although there’s no published evidence that the product actually works in animals or humans—other than the founders’ anecdotes.

“We did internally test ourselves against a blinded placebo product,” Abbott says. “It was a pretty grueling and fun experiment.” The company recommends drinking a vial of its probiotic right before or while consuming alcohol—which is why employees were handing them out at the nightclub on Saturday. Taking it the morning after a night of heavy drinking would be too late, Abbott says.

The start-up has also distributed more than 10,000 samples of the product and heard back from hundreds of people. About 94% said they perceived a benefit. “Which, of course, is not scientific data,” Oliver admits.

“I’d love to have the budget to launch full clinical trials and demonstrate efficacy,” Oliver says. “But being required to demonstrate efficacy is too much. I’d argue that would just kill innovation for bioproducts like this.”

The lack of formal tests in humans has helped the company move fast, but it raises questions about how far future biotech start-ups will be able to take their genetically engineered microbes without FDA review.

Several microbiome-oriented start-ups are already concocting nonengineered probiotics intended to clear up acne and other skin conditions. The ease of engineering microbes means that more start-ups like ZBiotics could start popping up.

ZBiotics began selling its product on its website last week starting at $36 for three 15 mL bottles. It got to this point on a lean budget. “Doing good microbiology doesn’t require much,” Oliver says. The firm raised its first $320,000 in 2016. ZBiotics later raised an additional $3.1 million, mostly from angel investors, after participating in the start-up accelerator Y Combinator.

The company says GMOs have gotten a bad rap for their lack of perceivable benefits to consumers. The genetically modified crops sold in the US are largely engineered for traits that protect them from insects and herbicides. Those traits are designed to increase yields and cut costs for farmers, but the benefit isn’t usually obvious to consumers.

Abbott and Oliver hope their product will help change public perception of GMOs. “We want to set the standard for transparency and safety and demonstrate a responsible approach for doing this,” Oliver says.

ZBiotics has ambitions for additional products as well. For example, Oliver has been working on a probiotic engineered to enhance the amount of lactose degraded in the gut.

Ultimately, Abbott says, the company is about putting genetic engineering in the hands of the people. “We are not saying it is antiaging or gut wellness or something you can’t evaluate yourself,” he says. “It is: Take this product today, and if you feel better tomorrow, then you’ve had a positive experience with genetic engineering.”

CORRECTION

The story was updated on Aug. 22, 2019, to identify ZBiotics' probiotic as a food rather than a supplement.

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Comments

Dr. Paul C. Li (August 27, 2019 10:08 PM)

Dear Honorable Ed. at C&EN: The chemical “disulfiram” is one of highly or widely used rubber accelerators known to rubber compounders all over the world. One can find its sales from rubber chemical suppliers in the US. It is not so expensive like a drug. Again, follow the prescriptive amount in dosing with “Dargering Black tea “ you may survive hangover when you are unfortunately getting involved if not, then quit drinking alcoholic fluid forever. Submitted to your attention by a retired life long chemist in rubber compounding technology.

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Dr. Paul C. Li (August 27, 2019 10:08 PM)

Dear Honorable Ed. at C&EN: The chemical “disulfiram” is one of highly or widely used rubber accelerators known to rubber compounders all over the world. One can find its sales from rubber chemical suppliers in the US. It is not so expensive like a drug. Again, follow the prescriptive amount in dosing with “Dargering Black tea “ you may survive hangover when you are unfortunately getting involved if not, then quit drinking alcoholic fluid forever. Submitted to your attention by a retired life long chemist in rubber compounding technology.